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A three base pair gene variation within the distal 5’‐flanking region of the interleukin‐10 (IL‐10) gene is related to the in vitro IL‐10 production capacity of lipopolysaccharide‐stimulated peripheral blood mononuclear cells Volume 15, numéro 2, June 2004

Auteurs
Sektion Humanparasitologie des Instituts fr Tropenmedizin, Eberhard‐Karls‐Universität, Tbingen, Germany Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon. Georg‐August‐Universität Göttingen, Zentrum fr Inner Medizin, Abteilung Hämatologie und Onkologie, Germany

Interleukin‐10 (IL‐10) is an important multifunctional immunmodulator. There is evidence that IL‐10 secretion is associated with certain genetic elements of the proximal IL‐10 gene 5’‐flanking region. The allelic and genotypic comparison of IL‐10 expression by lipopolysaccharide (LPS)‐ stimulated leukocytes (PBMC) with a recently discovered distal "indel" DNA‐sequence variation at ‐‐ 7400 bp revealed significant inter‐individual differences in the IL‐10 in vitro production capacity. Homozygotes lacking the three base pairs "GGA" (‐‐ 7400del) at this gene locus are characterised by high expression of IL‐10 with a median of 1690pg\ml ( P  0.009). The allelic comparison supports this finding ( P  0.002). Further analysis of the haplotype ‐‐ 7400\‐‐ 1087 showed that homozygotes for ‐‐ 7400del\‐‐ 1087G may be classified as very strong IL‐10 responders with a median IL‐10 secretion of 2378 pg\ml ( P  0.025). When leukocytes were stimulated in vitro by dibutyryl‐cAMP or infected with Epstein‐Barr virus no significant inter‐individual differences between the ‐‐ 7400indel alleles or genotypes and the IL‐10 in vitro production capacity were observed. Our findings further the understanding of the complexity of IL‐10 gene regulation in relation to defined regulatory gene variations.